Hereditary pheochromocytoma-paraganglioma is a term encompassing several distinct genetic disorders in which the two respective tumors appear. Mutations in succinate dehydrogenase (SDH) genes seem to play a pivotal role in the pathogenesis. Typical manifestations arise from excessive catecholamine secretion - hypertension, headaches, diaphoresis, anxiety, and palpitations are some of the most common. The detailed patient history, physical examination, biochemical tests, and imaging and genetic studies should be used to make an early diagnosis as a significant risk exists toward a malignant transformation of tumors and their metastatic spread.
The clinical presentation of hereditary pheochromocytoma-paraganglioma mainly depends on the secretory properties of the two tumors. A pheochromocytoma, arising from the adrenal medulla, almost always secretes catecholamines, whereas paragangliomas (arising from paravertebral neuroendocrine tissues) can be either parasympathetic and nonsecretory, or sympathetic and produce catecholamines as well    . The main feature of catecholamine hypersecretion is paroxysmal hypertension, which is encountered in virtually all patients    . Palpitations, tachycardia, arrhythmia, headaches, bouts of diaphoresis, and anxiety attacks are other frequent manifestations of this disease   . These manifestations are often induced when the individual changes his/her body position (for example, from sitting to standing) but surgery, exercise, and drug-induced manipulations of blood pressure may also serve as promoting factors   . Painless hematuria could be observed if paragangliomas are located within the urinary bladder wall . On the other hand, the cranial or neck localization of paragangliomas can result in a unilateral hearing loss, tinnitus, dysphagia, localized pain, impaired tongue movement, or even cough or hoarseness due to the mass effect of the spreading tumor . Head and neck paragangliomas, however, are rarely secretory and are much less likely to produce catecholamine-related symptoms    .
Because of the potential for malignant transformation of both pheochromocytomas and paragangliomas in this hereditary syndrome, it is critical to establish an early diagnosis. With a properly obtained patient history and a detailed physical examination, the physician can obtain sufficient information to indicate further testing. In addition to the onset of symptoms, as well as their course and progression, the patient interview might reveal incompletely explained sudden death within the family, which may favor a hereditary component in the presumptive diagnosis . During the physical examination, tachyarrhythmia and blood pressure changes can be observed .
Imaging studies are the cornerstone in recognizing the etiology of the disease. Computed tomography (CT) and magnetic resonance imaging (MRI) are the two main imaging procedures that are able to visualize the tumor location  . MRI, but also 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT scanning and 123I-metaiodobenzylguanidine (MIBG) scintigraphy are used for the detection of metastatic disease  .
Biochemical studies should be carried out to determine the concentration of catecholamines in the circulation. Measurements of serum free or urinary fractioned metanephrines through liquid chromatography-mass spectrometry (LC-MS) is regarded as the optimal laboratory procedure .
Finally, a distinction between different disorders where these two tumors appear is achieved through genetic studies. Revealed mutations of specific succinate dehydrogenase (SDH) genes are main criteria used to confirm the diagnosis of hereditary pheochromocytoma-paraganglioma  .